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Candida albicans is the most prevalent fungal pathogen associated with candidemia. Similar to other fungi, the complex life cycle of C. albicans has been challenging to study with high-resolution microscopy due to its small size. We employed ultrastructure expansion microscopy (U-ExM) to directly visualise sub-cellular structures at high resolution in the yeast and during its transition to hyphal growth. NHS-ester pan-labelling in combination with immunofluorescence (IF) via snapshots of various mitotic stages provided a comprehensive map of nucleolar and mitochondrial segregation dynamics and enabled the resolution of inner and outer plaque of spindle pole bodies (SPBs). Analyses of microtubules (MTs) and SPBs suggest that C. albicans displays side-by-side SPB arrangement with a short mitotic spindle and longer astral MTs (aMTs) at the pre-anaphase stage. Modifications to the established U-ExM protocol enabled the expansion of six other human fungal pathogens, revealing that the side-by-side SPB configuration is a plausible conserved feature shared by many fungal species. We highlight the power of U-ExM to investigate sub-cellular organisation at high resolution and low cost in poorly studied and medically relevant microbial pathogens.
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Circadian rhythms are biological rhythms that originate from the "master circadian clock," called the suprachiasmatic nucleus (SCN). SCN orchestrates the circadian rhythms using light as a chief zeitgeber, enabling humans to synchronize their daily physio-behavioral activities with the Earth's light-dark cycle. However, chronic/ irregular photic disturbances from the retina via the retinohypothalamic tract (RHT) can disrupt the amplitude and the expression of clock genes, such as the period circadian clock 2, causing circadian rhythm disruption (CRd) and associated neuropathologies. The present review discusses neuromodulation across the RHT originating from retinal photic inputs and modulation offered by endocannabinoids as a function of mitigation of the CRd and associated neuro-dysfunction. Literature indicates that cannabinoid agonists alleviate the SCN's ability to get entrained to light by modulating the activity of its chief neurotransmitter, i.e., γ-aminobutyric acid, thus preventing light-induced disruption of activity rhythms in laboratory animals. In the retina, endocannabinoid signaling modulates the overall gain of the retinal ganglion cells by regulating the membrane currents (Ca2+, K+, and Cl- channels) and glutamatergic neurotransmission of photoreceptors and bipolar cells. Additionally, endocannabinoids signalling also regulate the high-voltage-activated Ca2+ channels to mitigate the retinal ganglion cells and intrinsically photosensitive retinal ganglion cells-mediated glutamate release in the SCN, thus regulating the RHT-mediated light stimulation of SCN neurons to prevent excitotoxicity. As per the literature, cannabinoid receptors 1 and 2 are becoming newer targets in drug discovery paradigms, and the involvement of endocannabinoids in light-induced CRd through the RHT may possibly mitigate severe neuropathologies.
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Ritmo Circadiano , Endocannabinoides , Retina , Endocannabinoides/metabolismo , Endocannabinoides/fisiología , Humanos , Animales , Ritmo Circadiano/fisiología , Retina/fisiología , Retina/metabolismo , Núcleo Supraquiasmático/fisiología , Núcleo Supraquiasmático/efectos de los fármacosRESUMEN
The journal retracts the article, "A Novel Herbal Hydrogel Formulation of Moringa oleifera for Wound Healing" [...].
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Introduction T-type fractures of the acetabulum are uncommon injuries, typically resulting in poorer long-term outcomes compared to other patterns of acetabular fractures. Our main purpose is to analyse the epidemiology, functional outcomes, and factors affecting the functional outcomes of patients with T-type acetabular fractures. Methods This prospective, single-centre study included 73 patients with T-type and T with posterior wall acetabular fractures. They underwent treatment with open reduction internal fixation using plating through the modified Stoppa, Kocher-Langenbeck (KL), or dual approach. The post-operative reduction was assessed according to Matta's criteria, and functional outcomes were evaluated using the modified Harris hip score. Results Between September 2017 and January 2023, 53 patients underwent surgery for T-type fractures (72.6%), and 20 patients were treated for T with posterior wall acetabular fractures (27.4%). The minimum follow-up period was one year, with a mean follow-up of 3.5 years. Anatomical reduction emerged as the major contributing factor towards good functional outcomes compared to satisfactory reduction according to Matta's criteria (P value: 0.006). Overall, 65 patients (89%) achieved excellent to good modified Harris hip scores, while eight patients (11%) obtained fair to poor scores. Patients with T-type fractures demonstrated better functional outcomes compared to T with posterior wall fractures (P value: 0.031). Conclusion Anatomical reduction, as assessed by Matta's reduction criteria, serves as a predictor of favourable functional outcomes. T with posterior wall fractures exhibit poor outcomes in comparison to T-type fractures. The surgical approach employed does not influence the reduction or the final functional outcome of the patient.
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Glioblastoma, a highly lethal form of brain cancer, is characterized by its aggressive growth and resistance to conventional treatments, often resulting in limited survival. The response to therapy is notably influenced by various patient-specific genetic factors, underscoring the disease's complexity. Despite the utilization of diverse treatment modalities such as surgery, radiation, and chemotherapy, many patients experience local relapse, emphasizing the critical need for improved therapeutic strategies to effectively target these formidable tumors. Recent years have witnessed a surge in interest in natural products derived from plants, particularly alkaloids, for their potential anticancer effects. Alkaloids have shown promise in cancer chemotherapy by selectively targeting crucial signaling pathways implicated in tumor progression and survival. Specifically, they modulate the NF-κB and MAPK pathways, resulting in reduced tumor growth and altered gene expression across various cancer types. Additionally, alkaloids exhibit the capacity to induce cell cycle arrest, further impeding tumor proliferation in several malignancies. This review aims to delineate recent advances in understanding the pathology of glioblastoma multiforme (GBM) and to explore the potential therapeutic implications of alkaloids in managing this deadly disease. By segregating discussions on GBM pathology from those on alkaloid-based therapies, we provide a structured overview of the current challenges in GBM treatment and the promising opportunities presented by alkaloid-based interventions. Furthermore, we briefly discuss potential future directions in GBM research and therapy beyond alkaloids, including emerging treatment modalities or areas of investigation that hold promise for improving patient outcomes. In conclusion, our efforts offer hope for enhanced outcomes and improved quality of life for GBM patients through alkaloid-based therapies. By integrating insights from pathology and therapeutic perspectives, we underscore the significance of a comprehensive approach in addressing this devastating disease.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patología , Glioblastoma/terapia , Glioblastoma/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Alcaloides/uso terapéutico , Transducción de Señal/efectos de los fármacos , AnimalesRESUMEN
Eosinophilic esophagitis (EoE) is a chronic and progressive immune-mediated esophageal disorder. Given its increasing incidence, it is now a leading cause of dysphagia and food impaction in the United States. Eosinophilic esophagitis is most common in adult White men and has a high concurrence rate with other atopic conditions like allergic rhinitis, bronchial asthma, and eczema. The initial presentation includes symptoms of esophageal dysfunction, classically solid-food dysphagia. Without treatment, inflammation can progress to fibrosis with the formation of strictures, leading to complications such as food impaction. It is a clinicopathologic disease requiring compatible clinical symptoms and histologic evidence of eosinophil-predominant inflammation of the esophageal epithelium with more than 15 eosinophils per high-power field. The mainstay of management includes the 3 d's (diet, drugs, dilation): dietary modifications to eliminate trigger food groups; medications including proton pump inhibitors, swallowed topical glucocorticoids, and dupilumab; and esophageal dilation to manage strictures. Various elimination diets have been found to be effective, including 1-food, 2-food, 4-food, and 6-food elimination diets. Dupilumab, a humanized monoclonal antibody that regulates interleukin 4 and 13 signaling pathways, has shown promising results in clinical trials and was approved by the Food and Drug Administration in 2022 for use in EoE. Symptom alleviation, although important, is not the sole end point of treatment in EoE as persistent inflammation, even in the absence of symptoms, can lead to esophageal fibrosis and stricture formation over time. The chronic nature and high recurrence rates of EoE warrant maintenance therapy in patients with EoE after initial remission is achieved.
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Trastornos de Deglución , Esofagitis Eosinofílica , Gastroenterólogos , Masculino , Adulto , Humanos , Esofagitis Eosinofílica/diagnóstico , Esofagitis Eosinofílica/terapia , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Constricción Patológica/complicaciones , Constricción Patológica/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Fibrosis , Atención Primaria de Salud , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
INTRODUCTION: Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. METHODS: Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. RESULTS: A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. DISCUSSION: Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.
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INTRODUCTION: Burkholderia infection commonly presents as bacteraemic pulmonary disease; however, it is notorious for its wide variety of presentations in chronic cases, including musculoskeletal manifestations. It is common in patients living in endemic areas with comorbidities such as diabetes and who have chronic alcoholism. It was previously under-reported due to a low index of suspicion. Now, there is an increasing trend of diagnosis of these infections in non-endemic areas because of various factors, such as MALDI-TOF, molecular tests, and PCR. MATERIALS AND METHODS: This is a single tertiary centre study of 10 patients, diagnosed with Burkholderia infection and treated at our institution between 2021 and 2023 and followed up for a minimum of six months. Information was collected from outpatient and inpatient records. RESULTS: In this study, the mean age of the patients was 45 years, with eight males and two females. Out of 10, seven patients had comorbidities. However, only one patient has a history of travelling to an endemic area. All our patients were treated operatively, and the course of intervention and the planning of the surgical procedure were decided according to clinico-radiological findings. Six out of 10 patients suffering from Burkholderia species infections have a history of prolonged ICU stay, four of them tested positive for Burkholderia pseudomallei and the remaining two tested positive for Burkholderia cepacia, with a mean average time of 24.6 days. Diabetes was the most common comorbidity in 70% of the patients. The knee was the most commonly affected joint, showing involvement in 60% of patients. We have done surgical intervention in all patients. In our study, we have given IV antibiotics for a minimum of six weeks to all patients, followed by oral antibiotic therapy for three to six months on the basis of regular follow-up of clinico-haematologic parameters. CONCLUSION: Infections caused by Burkholderia species should be considered a potential causative agent of musculoskeletal infections in non-endemic areas without prior history of travelling to endemic areas. It may present with a chronic, mild course; a high index of suspicion is required, and it is important that due suspicion translates to prompt diagnosis and appropriate treatment to mitigate the course of the disease and associated morbidities in patients.
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Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.
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A comprehensive literature search was conducted in PubMed, Cochrane Library, Web of Science, Scopus, the National Library of Medicine (NLM) catalog, and Google Scholar from January 1980 up until October 2023 on plants in the Gundelia genus. Gundelia L. (Asteraceae) has been treated as a monospecific genus with Gundelia tournefortii L. (1753: 814) in most recent floras with wide variation in corolla color, but nowadays, the genus consists of 17 species. The unripe inflorescences of these species, especially G. tournefortii L., are consumed in many ways. 'Akkoub' or 'akko' in Arabic, "Kangar" in Persian, and "Silifa" in Greek are the common names of G. tournefortii L., also known as tumble thistle in English. They have been used in traditional medicine to treat bronchitis, kidney stones, diarrhea, stomach pain, inflammation, liver and blood diseases, bacterial and fungal infections, and mumps. Based on recent studies, their extracts have exhibited hepatoprotective, hypolipidemic, antioxidant, anti-inflammatory, and antimicrobial effects. Moreover, a variety of phytochemicals, including terpenoids, sterols, and fatty acids, as well as vitamins and minerals, have been identified in this genus. This study reviewed the ethnobotany, phytochemicals, and biological activities of the plants in the Gundelia genus as functional foods and herbal remedies.
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Asteraceae , Etnobotánica , Etnofarmacología , Fitoterapia , Medicina Tradicional , Extractos Vegetales/farmacología , Fitoquímicos/farmacologíaRESUMEN
The influence of chronic diseases on various facets of macrophage cellular senescence is poorly understood. This study evaluated the impact of chronic hyperglycemia on the induction of cellular senescence and subsequent immunosurveillance functions in RAW264.7 macrophages. Macrophages were cultured under normal glucose (NG; 5 mM), high glucose (HG; 20 mM), and very high glucose (VHG; 40 mM) conditions and assessed for markers of cellular senescence. Hyperglycemia induced strong upregulation of SA-ß-gal activity, and loss of PCNA and Lamin B1 gene expression while markers of cell cycle arrest generally decreased. Non-significant changes in SASP-related proteins were observed while ROS levels slightly decreased and mitochondrial membrane potential increased. Protein concentration on the exosome membrane surface and their stability appeared to increase under hyperglycemic conditions. However, when macrophages were exposed to the secretory media (SM) of senescent preadipocytes, a dramatic increase in the levels of all inflammatory proteins was recorded especially in the VHG group that was also accompanied by upregulation of NF-κB and NLRP3 gene expression. SM treatment to hyperglycemic macrophages activated the TLR-2/Myd88 pathway but decreased the expression of scavenger receptors RAGE, CD36, and Olr-1 while CD44 and CXCL16 expression increased. On exposure to LPS, a strong upregulation in NO, ROS, and inflammatory cytokines was observed. Together, these results suggest that primary markers of cellular senescence are aberrantly expressed under chronic hyperglycemic conditions in macrophages with no significant SASP activation. Nonetheless, hyperglycemia strongly deregulates macrophage functions leading to impaired immunosurveillance of senescent cells and aggravation of inflamm-aging. This work provides novel insights into how hyperglycemia-induced dysfunctions can impact the potency of macrophages to manage senescent cell burden in aging tissues.
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Senescencia Celular , Glucosa , Macrófagos , Animales , Senescencia Celular/efectos de los fármacos , Ratones , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Glucosa/metabolismo , Células RAW 264.7 , Hiperglucemia/metabolismo , Hiperglucemia/inmunología , Biomarcadores/metabolismo , Vigilancia Inmunológica , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.
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Enfermedad de Alzheimer , Vitamina D , Humanos , Señalización del Calcio , Calbindinas , Calmodulina , Calcio , Proteínas de Unión al Calcio , Canales de Calcio , Calcineurina , Proteína Quinasa Tipo 2 Dependiente de Calcio CalmodulinaRESUMEN
INTRODUCTION: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival. METHODS: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. RESULTS: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups. DISCUSSION: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.
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Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Masculino , Humanos , Anciano , Femenino , Esófago de Barrett/cirugía , Esófago de Barrett/patología , Estudios Prospectivos , Neoplasias Esofágicas/patología , Adenocarcinoma/patología , Endoscopía GastrointestinalRESUMEN
BACKGROUND AND AIMS: Although gastroesophageal reflux disease (GERD) symptoms are an essential criterion for Barrett's esophagus (BE) screening in most gastroenterology society guidelines, a significant proportion of BE and esophageal adenocarcinoma (EAC) cases do not endorse them. In a systematic review and meta-analysis, we aimed to study the prevalence of BE/EAC in those with and without GERD. METHODS: A systematic search was conducted through 5 major databases for studies reporting prevalence of BE/EAC in patients with and without GERD. Pooled proportions and odds ratios (ORs) of BE, long-segment BE, short-segment BE, dysplasia, and EAC in patients with and without GERD were synthesized. RESULTS: Forty-three articles (12,883 patients with GERD; 51,350 patients without GERD) were included in the final analysis. BE prevalence was 7% (95% confidence interval [CI], 5.8%-8.5%) and 2.2% (95% CI, 1.6%-3%) among individuals with and without GERD, respectively. EAC prevalence was 0.6% (95% CI, 0.4%-1%) and 0.1% (95% CI, 0%-0.2%) in those with and without GERD, respectively. The overall risks for BE (OR, 2.91; 95% CI, 2.06-4.11) and long-segment BE (OR,4.17; 95% CI, 1.78-9.77) were higher in patients with GERD, but the risk for short-segment BE (OR, 1.77; 95% CI, 0.89-3.52) did not differ between the two groups. In 9 population-based high-quality studies (2244 patients with GERD; 3724 patients without GERD), BE prevalence in patients without GERD was 4.9% (95% CI, 2.6%-9%). BE prevalence was highest in North American studies (10.6% [GERD] and 4.8% [non-GERD]). CONCLUSIONS: BE prevalence in those without GERD is substantial, particularly in large high-quality population-based studies. These data are important to factor in future BE/EAC early detection guidelines.
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Background In order to maintain the surgery site's shape, functionality, and aesthetics, closure of the wound is essential for intra-oral and general surgical procedures. Wound closure speeds up healing by reducing the buildup of inflammatory cells. For a wound to heal well, the incision must be precise, the tissue must be handled delicately, the wound must be precisely repositioned, and the closure material must have optimum functional properties and be sterile. Aim This study aims to conduct a clinical comparison of the effectiveness of silk suture versus isoamyl 2-cyanoacrylate (IAC) for intra-oral mucosal incisions. Methodology Fifty patients who needed a minor oral surgical operation under local anesthesia from the Department of Oral and Maxillofacial Surgery were recruited for this prospective clinical trial. Ethical clearance and informed consent were obtained for this study. Two groups were created from the sample of 50 patients in this investigation. An intra-oral mucosal incision was closed in one group using a 3-0 silk suture and in the second using two drops of IAC. An accurate approximation of the incised edges was used to avoid leaving any gaps between them. Parameters such as the time taken for closure, pain, bleeding, swelling, mouth opening, wound dehiscence, wound infection, and local ulceration were evaluated in this study. A visual analog scale (0-10) was used to assess the pain score. Facial swelling was evaluated by the tape method given by Gabka and Matsumura. The measurement was done from tragus to pogonion, tragus to oral commissure, and outer canthus to gonion. The sum of these measurements was calculated. By measuring the distance between the incisal edges of the upper and lower central incisors, the trismus was evaluated using a graduated metal scale. Assessment of bleeding (0-4) was done by asking the patient. Assessment of wound dehiscence and local ulceration was done based on visual inspection and palpation on the first, second, and seventh days postoperatively. All the recorded parameters were tabulated. The statistical analysis was done using SPSS version 25.0 (IBM Corp., Armonk, NY). The Chi-square test was used to compare the categorical variables between the study groups. The independent t-test was used to compare the means between the study groups. The statistical significance was kept at a p-value less than 0.05. Results The results showed that there was no statistically significant difference between suture and IAC in terms of incidence of pain and wound dehiscence. But the time taken for wound closure was less with IAC, and the pain score on the seventh day was higher with IAC and statistically significant. Conclusion We observed that IAC was as effective as the gold standard silk suture. The advantages of IAC are its hemostatic and bacteriostatic qualities, and IAC also took less time to complete the procedure.
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Aim The study compared the anesthetic effectiveness of articaine and lignocaine when premolars are extracted bilaterally for orthodontic purposes. Material and methods This prospective split-mouth study was performed on 30 cases selected from orthodontic referral patients reporting to the Oral and Maxillofacial Surgery Department at Maharaja Ganga Singh Dental College and Research Center, Rajasthan, India, for bilateral extraction of premolars under local anesthesia. We used 4% articaine hydrochloride and adrenaline 1:100000 (AH) as group A and 2% lignocaine hydrochloride with adrenaline 1:100000 (LH) on the control side as group B. For premolar anesthetization, 0.6-1.6 ml of AH and 1-2 ml of LH were injected submucosally in the buccal vestibular area. The extraction procedure was then carried out after achieving adequate anesthesia. The pain was assessed with Visual Analog Scale. The average onset time and duration of anesthesia were recorded. Data collected were summarized with descriptive statistics. The SPSS version 23.0 (IBM Corp., Armonk, New York) was used for data entry, validation, and analysis. Means of continuous variables were compared using the student t-test. All tests were 2-tailed and significant at equal or less than 0.05. (p≤0.05). Results When comparing the overall anesthetic efficiency, Group A had a lower overall pain score of 0.43 while Group B had a higher overall pain score of 2.9. The average onset time of anesthesia in Group A was 1.2 minutes and 2.55 minutes in Group B. In Group A, the average duration of anesthesia was 70 minutes, and 46.5 minutes in Group B. These parameters were statistically significant with a p-value of <0.05. Conclusion The study concluded that as an alternative to lignocaine, articaine could be used effectively for maxillary premolar extractions for orthodontic reasons obviating palatal injection which is very painful to the patient.
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Fungi in the basidiomycete genus Malassezia are the most prevalent eukaryotic microbes resident on the skin of human and other warm-blooded animals and have been implicated in skin diseases and systemic disorders. Analysis of Malassezia genomes revealed that key adaptations to the skin microenvironment have a direct genomic basis, and the identification of mating/meiotic genes suggests a capacity to reproduce sexually, even though no sexual cycle has yet been observed. In contrast to other bipolar or tetrapolar basidiomycetes that have either two linked mating-type-determining (MAT) loci or two MAT loci on separate chromosomes, in Malassezia species studied thus far the two MAT loci are arranged in a pseudobipolar configuration (linked on the same chromosome but capable of recombining). By generating additional chromosome-level genome assemblies, and an improved Malassezia phylogeny, we infer that the pseudobipolar arrangement was the ancestral state of this group and revealed six independent transitions to tetrapolarity, seemingly driven by centromere fission or translocations in centromere-flanking regions. Additionally, in an approach to uncover a sexual cycle, Malassezia furfur strains were engineered to express different MAT alleles in the same cell. The resulting strains produce hyphae reminiscent of early steps in sexual development and display upregulation of genes associated with sexual development as well as others encoding lipases and a protease potentially relevant for pathogenesis of the fungus. Our study reveals a previously unseen genomic relocation of mating-type loci in fungi and provides insight toward the identification of a sexual cycle in Malassezia, with possible implications for pathogenicity.
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Basidiomycota , Malassezia , Humanos , Malassezia/genética , Evolución Molecular , Basidiomycota/fisiología , Hongos/genética , Filogenia , Reproducción/genética , Genes del Tipo Sexual de los Hongos/genéticaRESUMEN
This review explores the potential of photonic nanoparticles for cancer theranostics. Photonic nanoparticles offer unique properties and photonics capabilities that make them promising materials for cancer treatment, particularly in the presence of near-infrared light. However, the size of the particles is crucial to their absorption of near-infrared light and therapeutic potential. The limitations and challenges associated with the clinical use of photonic nanoparticles, such as toxicity, immune system clearance, and targeted delivery to the tumor are also discussed. Researchers are investigating strategies such as surface modification, biodegradable nanoparticles, and targeting strategies to improve biocompatibility and accumulation in the tumor. Ongoing research suggests that photonic nanoparticles have potential for cancer theranostics, further investigation and development are necessary for clinical use.
Tiny particles called 'photonic nanoparticles' can be used to help treat cancer. These particles have special properties that allow them to be used with special light to treat cancer. However, the size of the particles is really important, so scientists are trying to find ways to make sure they are the right size. There are also some challenges with using these particles in people, like making sure they don't harm the body and that they go to the right place. Scientists are working on ways to improve the safety of these particles and make sure they go where they need to.
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Nanopartículas del Metal , Nanopartículas , Neoplasias , Humanos , Medicina de Precisión , Óptica y Fotónica , Nanomedicina Teranóstica , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológicoRESUMEN
Fungi in the basidiomycete genus Malassezia are the most prevalent eukaryotic microbes resident on the skin of human and other warm-blooded animals and have been implicated in skin diseases and systemic disorders. Analysis of Malassezia genomes revealed that key adaptations to the skin microenvironment have a direct genomic basis, and the identification of mating/meiotic genes suggests a capacity to reproduce sexually, even though no sexual cycle has yet been observed. In contrast to other bipolar or tetrapolar basidiomycetes that have either two linked mating-type-determining ( MAT ) loci or two MAT loci on separate chromosomes, in Malassezia species studied thus far the two MAT loci are arranged in a pseudobipolar configuration (linked on the same chromosome but capable of recombining). By incorporating newly generated chromosome-level genome assemblies, and an improved Malassezia phylogeny, we infer that the pseudobipolar arrangement was the ancestral state of this group and revealed six independent transitions to tetrapolarity, seemingly driven by centromere fission or translocations in centromere- flanking regions. Additionally, in an approach to uncover a sexual cycle, Malassezia furfur strains were engineered to express different MAT alleles in the same cell. The resulting strains produce hyphae reminiscent of early steps in sexual development and display upregulation of genes associated with sexual development as well as others encoding lipases and a protease potentially relevant for pathogenesis of the fungus. Our study reveals a previously unseen genomic relocation of mating-type loci in fungi and provides insight towards the discovery of a sexual cycle in Malassezia , with possible implications for pathogenicity. Significance Statement: Malassezia , the dominant fungal group of the mammalian skin microbiome, is associated with numerous skin disorders. Sexual development and yeast-to-hyphae transitions, governed by genes at two mating-type ( MAT ) loci, are thought to be important for fungal pathogenicity. However, Malassezia sexual reproduction has never been observed. Here, we used chromosome-level assemblies and comparative genomics to uncover unforeseen transitions in MAT loci organization within Malassezia , possibly related with fragility of centromeric-associated regions. Additionally, by expressing different MAT alleles in the same cell, we show that Malassezia can undergo hyphal development and this phenotype is associated with increased expression of key mating genes along with other genes known to be virulence factors, providing a possible connection between hyphal development, sexual reproduction, and pathogenicity.
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Nanomaterials have been the focus of intensive development and research in the medical and industrial sectors over the past several decades. Some studies have found that these compounds can have a detrimental impact on living organisms, including their cellular components. Despite the obvious advantages of using nanomaterials in a wide range of applications, there is sometimes skepticism caused by the lack of substantial proof that evaluates potential toxicities. The interactions of nanoparticles (NPs) with cells of the immune system and their biomolecule pathways are an area of interest for researchers. It is possible to modify NPs so that they are not recognized by the immune system or so that they suppress or stimulate the immune system in a targeted manner. In this review, we look at the literature on nanomaterials for immunostimulation and immunosuppression and their impact on how changing the physicochemical features of the particles could alter their interactions with immune cells for the better or for the worse (immunotoxicity). We also look into whether the NPs have a unique or unexpected (but desired) effect on the immune system, and whether the surface grafting of polymers or surface coatings makes stealth nanomaterials that the immune system cannot find and get rid of.